J Clinic Periodontology - 2019 - Ucak Turer - Clinical Evaluation of Injectable Platelet Rich Fibrin With Connective Tissue

Received: 25 July 2019 | Revised: 29 August 2019 | Accepted: 9 September 2019
DOI: 10.1111/jcpe.13193
CLINICAL PERIODONTOLOGY
Clinical evaluation of injectable platelet‐rich fibrin with

connective tissue graft for the treatment of deep gingival
recession defects: A controlled randomized clinical trial
Onur Ucak Turer1 | Mustafa Ozcan1 | Bahar Alkaya1 | Seren Surmeli1 |

Gulsah Seydaoglu2 | Mehmet Cenk Haytac1
1
Department of Periodontology, Cukurova
University, Adana, Turkey Abstract
2
Department of Biostatistics, Cukurova Aim: The aim of this study was to determine whether the combined connective tissue
University, Adana, Turkey
graft (CTG) with injectable platelet‐rich fibrin (i‐PRF) with coronally advanced flap
Correspondence (CAF) improved root coverage of deep Miller Class I or II gingival recessions com‐
Onur Ucak Turer, Department of
pared with CTG alone with CAF.
Periodontology, Faculty of Dentistry,
Cukurova University, Balcali, Adana, Turkey. Material and Methods: Seventy‐two patients with Miller class I and II gingival reces‐
Email: [email protected]
sions were enrolled. Thirty‐six patients were randomly assigned to the test group
(CAF+CTG+i‐PRF [700 rpm for 3 min]) or control group (CAF+CTG). Clinical evalua‐
tions were made at 6 months.
Results: At 6 months, complete root coverage was obtained at 88% of the sites treated
with CAF+CTG+i‐PRF and 80% of the sites treated with CAF+CTG. Difference be‐
tween the two groups was not statistically significant. At 6 months, the recession
depth (RD) reduction and increase in keratinized tissue height (KTH) of the test sites
were significantly better compared with the control sites.
Conclusions: According to the results, the addition of i‐PRF to the CAF+CTG treat‐
ment showed further development in terms of increasing the KTH and decreasing
RD. However, this single trial is not sufficient to advocate the true clinical effect of
i‐PRF on recession treatment with CAF+CTG and additional trials are needed.
KEYWORDS
connective tissue graft, injectable platelet‐rich fibrin, root coverage
1 | I NTRO D U C TI O N predictable RC method and CTG might increase the probability of

CRC, inconsistent CRC outcomes (18.1% to 86.7%) and limited re‐
The goals of plastic periodontal surgical (PPS) procedures for the generation of the missing attachment apparatus have been reported
treatment of gingival recessions (GR) are obtaining complete root after the use of CAF+CTG (Chambrone et al., 2010; Keceli, Kamak,
coverage (RC) and optimal aesthetic appearance. The gold stand‐ Erdemir, Evginer, & Dolgun, 2015). Therefore, many materials ca‐
ard of RC procedures is the coronally advanced flap (CAF) com‐ pable of stimulating tissue regeneration, have been proposed to
bined with connective tissue graft (CTG) (Aroca, Keglevich, Barbieri, improve outcomes for obtaining the best healing results (Cairo et
Gera, & Etienne, 2009; Cairo, Nieri, & Pagliaro, 2014; Dai, Huang, al., 2014; Eren & Atilla, 2012, 2014; Jankovic, Zoran, Iva, & Bozidar,
Ding, & Chen, 2019; Tonetti, Jepsen, & Working Group 2014 of the 2010; Jenabian, Motallebnejad, Zahedi, Sarmast, & Angelov, 2018;
European Workshop on Periodontology, 2014). Although CAF is a Keceli et al., 2015; Kuka, Ipci, Cakar, & Yılmaz, 2018).
72 | © 2019 John Wiley & Sons A/S. wileyonlinelibrary.com/journal/jcpe J Clin Periodontol. 2020;47:72–80.
Published by John Wiley & Sons Ltd
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UCAK TURER et al. | 73
The use of plasma that is rich in growth factors (GFs) for tissue re‐
generation in PPS has been proposed (Aroca et al., 2009; Huang, Neiva,
Clinical Relevance
Soehren, Giannobile, & Wang, 2005, Moraschini and Barboza, 2016).
Scientific rationale for the study: No study has compared the
Studies have demonstrated that the GFs in the plasma concentrates
use of CAF+CTG+i‐PRF with CAF+CTG for the treatment
stimulate the repair and regeneration of soft and hard tissues and that
of gingival recession.
the plasma reduces inflammation and subsequent pain and discomfort
Principal findings: This randomized clinical study showed
(Moraschini and Barboza, 2016, Castro et al., 2017; Miron et al., 2017).
that CAF+CTG+i‐PRF technique can provide additional
Platelet‐rich plasma (PRP) is a fraction of plasma that provides a rich
benefit in terms of KTH, RD reduction and the probability
source of GFs. While initial experiments revealed PRP contained high
of obtaining CRC for the treatment of deep Miller class I
concentrations of autologous GFs including platelet‐derived GF, vas‐
and II gingival recessions.
cular endothelial GF and transforming GF‐beta, PRF has since been
Practical implications: This study supports the effective‐
shown to release even higher total GFs over a more extended period
ness of CAF+CTG+i‐PRF surgical approach in the treat‐
of time (Aroca et al., 2009; Castro et al., 2017; Miron et al., 2017).
ment of deep gingival recession. The described technique
Major advantages of PRF include having completely immune‐com‐
is highly effective in obtaining KTH and RD reduction.
patible GFs collected at relatively no costs without anticoagulants
(Castro et al., 2017). Clinical use of PRF has been widely adopted in
the treatment of GRs; however, the results are contradictory (Aroca et
ethics committee. The study was registered at www.clinicaltrials.gov
al., 2009; Eren & Atilla, 2012, 2014; Gupta et al., 2015; Jankovic et al.,
as NCT04032405. This study was supported by Cukurova University
2010; Keceli et al., 2015; Kuka et al., 2018; Thamaraiselvan, Elavarasu,
Research Fund, Project: TSA‐2018‐10749)
Thangakumaran, Gadagi, & Arthie, 2015; Tunalı et al., 2015).
All participants had to meet the following inclusion criteria
Initial PRF formulations lacked a liquid concentrate of proteins, as
(Zucchelli, Marzadori, Mounssif, Mazzotti, & Stefanini, 2014):
standardized PRF contains the majority of GF concentration encap‐
sulated within its fibrin matrix (FM). Therefore, major developments
• ≥19 years of age,
and advancements were recently made with the aim of developing a
• Periodontally and systemically healthy,
liquid formulation of PRF (i‐PRF) (Miron et al., 2017). Recent studies
• FMPS and FMBS <15%,
have shown that despite slight or no increases in blood cell concen‐
• Presence of deep Miller Class I/II GR defect (≥3 mm in depth) at
trations and growth factors; i‐PRF was capable of inducing higher cell
the buccal aspect of incisors and canines,
migration and mRNA expression of TGF‐β, PDGF, osteocalcin and sig‐
• Presence of identifiable CEJ (step ≤1 mm at CEJ level and/or
nificant increase in type I collagen gene expression when compared
presence of a root irregularity/abrasion with identifiable CEJ, was
to PRP (Miron et al., 2019) and the blood clot (Varela et al., 2019). It
accepted),
has been suggested that i‐PRF provides a three‐dimensional fibrin clot
• No previous periodontal surgery.
network embedding platelets, leucocytes, type I collagen, osteocalcin
• Study exclusion criteria:
and growth factors (Varela et al., 2019) acting as a dynamic gel with
• Smoking,
additional release of growth factors up to 10 days (Miron et al., 2017).
• Contraindications for surgery,
To the best of our knowledge, this is the first study which at‐
• Presence of recession defects associated with caries, deep abra‐
tempts to use the i‐PRF clot as a scaffold for the CTG in order to
sion, restoration or pulpal pathology.
obtain a novel biomaterial, incorporating active GFs and live connec‐
tive tissues in a single framework. Therefore, the aim of this study
wass to determine whether the combination of CTG and autologous
2.1 | Experimental design
i‐PRF with CAF can improve the RCof isolated deep Miller Class I or
II GRs compared to CTG alone with CAF. This study was a double‐masked, randomized, controlled clinical
trial, with parallel design, comparing bilaminar techniques, consisting
of CAF+CTG, with and without i‐PRF application in the treatment of
2 | M ATE R I A L S A N D M E TH O DS deep (≥3 mm) recessions affecting the incisors. Each patient contrib‐
uted to one recession. Protocol phases were followed as previously
Seventy‐two subjects, 37 male and 35 female affected by GR in described (Zucchelli et al., 2014).
the upper and lower incisors were included in the study. The pa‐
tients were selected among individuals referred to Periodontology
2.2 | Sample size
Department of Cukurova University, between November 2017
and September 2018. The study protocol, questionnaires and in‐ The study was powered to detect a minimum clinically significant
formed consent in full accordance with the ethical principles of the difference of 0.8 mm in RD levels using α = .05, a power = %95, a
Declaration of Helsinki, as revisited in 2000, were approved by the hypothesized within‐group sigma of 1.1 mm, obtained from previous
Institutional Review Board and received the approval of the local studies (Cardaropoli, Tamagnone, Roffredo, & Gaveglio, 2012; Keceli
74 | UCAK TURER et al.
(a) (b) (c)
(d) (e) (f)
F I G U R E 1 Surgical technique in the test treated (CAF+CTG+i‐PRF) gingival defects. (a) 5 mm deep and 4 mm wide gingival recession
affecting the mandibular left canine. (b) CTG soaked with i‐PRF liquid gel. (c) Note the i‐PRF clot covering all surfaces of CTG. (d) After flap
elevation, the CTG+i‐PRF framework was sutured over the root surface, at the coronal level of the CEJ. (e) The flap was coronally advanced
to cover CTG+i‐PRF completely. (f) Intra‐oral view of the buccal recession site after 6 months
et al., 2015; Zucchelli et al., 2014). As a minimum, 30 patients per recession defects was not scheduled until the patient could dem‐
treatment arm were needed. In order to balance possible dropouts, onstrate an adequate standard of plaque control. All measure‐
36 patients were included in both groups. ments were carried out by a single masked examiner (S.S.). This
examiner was unaware of the treatment assignment and surgeries.
Measurement of recession depth (RD), as the distance between the
2.3 | Randomization
CEJ and gingival margin, was repeated three times by the examiner
Patients were assigned to one of the treatment groups with the use for a total of 50 defects with an intra‐agreement coefficient K of
of a computer‐generated randomization table. Each patient par‐ 0.86.
ticipated in only one recession defect. Allocation concealment was Full mouth plaque (FMPS) and bleeding (FMBS) scores were
obtained using sealed coded opaque envelopes containing the treat‐ recorded as the percentage of total surfaces (Ainamo & Bay 1975;
ment to the specific subject. The envelope was opened during the O'Leary, Drake, & Naylor,1972). The following clinical measurements
surgery after the treatment of the root surfaces. were taken 1 week before the surgery and at the 6‐month follow‐up
visit (Figures 1a and 2a):
2.4 | Initial therapy and clinical measurements

• GR depth (RD)
Following the screening, all subjects received prophylaxis session, • GR width (RW) (measured at the CEJ)
scaling and professional tooth cleaning. Surgical treatment of the • probing depth (PD)
F I G U R E 2 Surgical technique in the

control‐treated (CAF+CTG) gingival
defects. (a) 4 mm deep and 3 mm wide
gingival recession affecting the maxillary
left canine. (b) After flap elevation, the
CTG was sutured over the root surface,
at the coronal level of the CEJ. (c) The
flap was coronally advanced to cover the
CTG completely. (d) Intra‐oral view of the
buccal recession site after 6 months
(a) (b)
(c) (d)
• clinical attachment level (CAL) Mechanical and chemical treatment of root surfaces was per‐
• keratinized tissue height (KTH) (measured from the mucogingival formed as previously described (Zucchelli et al., 2010).
junction to the gingival margin)
• gingival thickness (GT) (determined with a caliper accurate to the
2.6 | i‐PRF and CTG – i‐PRF preparation
nearest 0.1 mm 1.5 mm apical to the gingival margin)
Before graft harvesting in the test sites, intravenous blood was col‐
RD, PD, CAL and KTH measurements were performed at the lected in two tubes of 10‐ml without anticoagulant and centrifuged
midbuccal aspect of the teeth, by a manual probe and were rounded immediately at 700 rpm for 3 min (60 g) at room temperature (Duo
up to the nearest millimetre (Zucchelli et al., 2009, 2010). Centrifuge, Process for PRF). The upper liquid layer was collected
as i‐PRF (Miron et al., 2017).
Then, the harvested CTG stayed in i‐PRF liquid for 15 min
2.5 | Surgical techniques
(Figure 1b). At the end, the i‐PRF clot enclosed the CTG similar to a
All surgeries were performed by the same expert periodontist scaffold (Figure 1c) and the graft was sutured on the recipient site
(O.U.T.). The labelled envelope containing the name of the interven‐ (Figure 1d). In the control group, CTG was applied without i‐PRF
tion was opened during surgery immediately after the treatment (Figure 2b). After CTG suturing, the flap was coronally advanced and
of the root surfaces. A bilaminar (CAF+CTG) technique was per‐ stabilized by sling sutures at the level of the CEJ for both test and
formed in both groups to accomplish RC (Zucchelli, Amore, Sforza, control groups (Figures 1e and 2c).
Montebugnoli, & Sanctis, 2003).
The surgeon chose the harvesting site on the palate on the
2.7 | Postsurgical instructions and infection control
basis of the amount and quality of tissue (Zucchelli et al., 2010), and
CTG was obtained by means of the disepithelization of a FGG with Postoperative pain/oedema was controlled with ibuprofen, 600 mg
diode laser as described in our previous study (Ozcelik, Seydaoglu, & at the beginning of the surgical procedure and subsequent doses if
Haytac, 2016). The width of the graft was chosen according to the needed. Patients recorded the quantity of analgesics taken during
amount of tissue required to cover the exposed root and 3 mm of the 1st week postsurgery. Patients were instructed not to brush their
connective tissue mesial and distal to it. teeth in the treated area but to spray with chlorhexidine solution
FIGURE 3 The CONSORT flowchart diagram of the study
(0.12%) for 2 weeks. Following this period, plaque control was main‐ between independent groups and paired t test was used for depend‐
tained by atraumatic toothbrushing. Patients were clinically ob‐ ent groups when the hypothesis was fulfilled; Mann–Whitney U test
served once a month for the following 6 months (Figures 1f and 2d). and Wilcoxon test were used when the hypothesis was not fulfilled.
Categorical measurement was analysed by Chi‐square test. A p‐
value <.05 considered as significant in all tests. Data expressed were
2.8 | Patient evaluation of postoperative morbidity
means ± SDs for continuous variables and percentages for categori‐
Postoperative pain was indirectly evaluated on the basis of the cal variables. All analyses were conducted using SPSS for Windows
mean consumption (in mg) of analgesics (Wessel & Tatakis, 2008; software (ver 22.0; IBM Inc).
Zucchelli et al., 2010). A questionnaire was given to each patient
and divided into two parts to be completed in different time
periods: 3 | R E S U LT S
• Regarding the postoperative discomfort and bleeding was com‐ A total of 72 patients (mean age 37.5 ± 12.6, min:20–max:58, for
pleted 1 week after the surgery based on a visual analogic scale CAF+CTG and 38.0 ± 11.2, min:19–max:58, for CAF+CTG+i‐PRF)
(VAS) (Cortellini et al., 2009; Zucchelli et al., 2010). were treated without any uneventful healing effects. The CONSORT
• Concerning patient aesthetic satisfaction in terms of RC, based on flowchart diagram showing for each group, the numbers of partici‐
a VAS, was completed at the 6‐months follow‐up visit. pants who were randomly assigned, received the intended treat‐
ments, and analysed for the primary outcome is reported in Figure 3.
Seven patients did not comply with the control. The data of these
2.9 | Objective evaluation of aesthetics
dropout patients were not included in the per‐protocol statistical
Objective evaluation of RC (Zucchelli et al., 2014) was scored at analysis. Therefore, the data of 65 defects were analysed. The base‐
the 6‐month postsurgical evaluation visit by an expert periodontist line and 6th‐month values of the clinical parameters are summarized
(M.C.H.) on a VAS. He was independent of the clinical examiner and in Table 1.
did not perform the surgeries. RD: Significant decrease was observed in both groups at
6 months compared with the baseline (p < .01). A significant differ‐
ence was found between groups at 6 months with a higher RD re‐
2.10 | Statistical analysis
duction in the test group (p = .05).
Kolmogrov–Smirnov test was used to evaluate if the quantita‐ PD: PD scores did not show any remarkable change at any point
tive measurements showed normal distribution. t Test was used in the study period for both groups.
TA B L E 1 Descriptive statistics for the clinical parameters Mean RC (MRC): No significant differences were found between
measured at baseline and 6 months groups (97% and 95% in the test and control group, respectively)
CAF+CTG CAF+CTG+i‐PRF (p = .315).

(n = 31) (n = 34) Complete RC (CRC): CRC was achieved in 30 out of 34 (88%) and
in 25 out of 31 (80%) gingival defects in the test and control group,
Mean ± SD Mean ± SD p
respectively. A slight (though statistically not significant, p = .396)
PD superiority was observed for the CAF+CTG+i‐PRF treated patients
Baseline 1.58 ± 0.50 1.50 ± 0.50 .522 in terms of CRC parameter.
6th month 1.29 ± 0.46* 1.35 ± 0.48 .597 Postoperative painkiller consumption, bleeding, discomfort and
CAL aesthetic evaluations are reported in Table 2. Significant differences
Baseline 5.5 ± 1.2 5.4 ± 0.9 .443 between groups were found in VAS discomfort, with higher scores
th
6 month 1.6 ± 0.7* 1.5 ± 0.6* .420 in the control group (p < .03). There were no significant differences
RW between groups for “patients’ and periodontist's VAS evaluation of
Baseline 3.8 ± 1.1 4.2 ± 1.3 .162

root coverage” (p > .05).
th
6 month 0.4 ± 1.2* 0.2 ± 0.6* .334
RD
4 | D I S CU S S I O N
Baseline 4.0 ± 1.0 3.9 ± 0.8 .702
6th month 0.4 ± 0.7* 0.1 ± 0.3* .050
The use of autologous plasma that is rich in GFs is increasing as an
KTH
adjunct biomaterial in PPS (Moraschini and Barboza, 2016). However,
Baseline 2.0 ± 1.1 2.0 ± 1.3 .961 the benefits of PRF are still controversial and there is no data about
6th month 4.0 ± 1.3* 4.8 ± 1.2* .017 using i‐PRF form on the treatment of GR. Therefore, the main goal of
GT the current study was to evaluate the effects of adjunctive i‐PRF ap‐
Baseline 0.9 ± 0.3 0.8 ± 0.3 .762 plication as a scaffold for CTG together with CAF on the height and
th
6 month 1.6 ± 0.7* 1.7 ± 0.6* .356 thickness of keratinized tissue and on RCattained for single Miller
MRC Class I/II deep recession defects of anterior teeth. The results dem‐
th
6 month 94.6 ± 11.9 97.1 ± 8.3 .315 onstrated that both techniques (CAF+CTG and CAF+CTG+i‐PRF)
were effective in reducing GR, while clinically superior RD reduction
CRC**
and KTH increase were achieved at 6 months in the CAF+CTG+i‐
6th month 25 (80.6%) 30(88.2%) .396
PRF treated GRs as well as better VAS discomfort scores in the early
*p < .01 between baseline and 6th month, ** n and %.
healing period.
Large evidence supports that the CAF+CTG achieved the best
CAL: Significant (p < .01) decrease was observed in both groups clinical outcomes in single GRs (Cairo et al., 2014; Paolantonio,
at 6 months compared with the baseline, with no significant differ‐ 2002; Pini Prato et al., 2000). The CRC results of the control group
ences between groups. (CAF+CTG) in the present study (%80) were similar with the litera‐
KTH: Significant increase was observed in both groups at ture, which indicate an increase in the KTH (Cheung & Griffin, 2004;
6 months compared with the baseline (p < .01). Significantly higher Zucchelli et al., 2014, 2010).
values were measured in the test group compared with controls The results of a recent meta‐analysis (Moraschini and Barboza,
(p < .01). 2016) suggested that the use of PRF membranes did not improve the
GT: Significant (p < .05) increase was observed in both groups RC, KTH or CAL in the treatment of Miller Class I/II GRs compared
compared with the baseline, while no significant differences were with other treatment modalities. Several studies compared CAF+PRF
found between groups. with CAF procedure and reported no additional benefit in terms of
TA B L E 2 Postoperative painkiller
CAF+CTG CAF+CTG+i‐PRF
assumption, morbidity and aesthetic
evaluations Mean ± SD Mean ± SD p
Painkiller consumption 1,193.5 ± 459.6 1,058.8 ± 320.1 .172

Patient VAS evaluation
Discomfort 8.5 ± 0.8 8.1 ± 0.8 .035
Bleeding 7.9 ± 0.7 8.0 ± 0.7 .601
Root coverage 9.5 ± 0.9 9.7 ± 0.5 .160
Periodontist VAS evaluation
Root coverage 9.2 ± 1.3 9.6 ± 0.8 .099
mean RC or short‐term wound healing for the treatment of multiple biological processes subsequently help in the stabilization of CTG in
GRs. The only superior effect of PRF was shown on tissue thickness the early healing period, which is considered to be a crucial factor for
parameter (Aroca et al., 2009; Kuka et al., 2018). The other group of the success of mucogingival treatment.
studies compared the CAF+CTG with CAF+PRF and showed similar Recently, it has been proposed that original i‐PRF preparation
results for both groups (Eren & Atilla, 2014; Jankovic et al., 2010; protocol (as used in the current study) is neither adequately effective
Tunalı et al., 2015). Recently, Keceli et al. (2015) evaluated the ef‐ at separating cell types or producing high yields of platelets/leuco‐
fectiveness of CAF+CTG+PRF compared with CAF+CTG and con‐ cytes (Miron et al., 2019). Therefore, several modifications of i‐PRF
cluded that additional PRF did not further develop the outcomes of preparation, such as 600 rpm/8 min/44 g (Al‐Maawi et al., 2018) and
CAF+CTG treatment except increasing the GT (Keceli et al., 2015). 2,700 rpm/3 min/408 g (Castro et al., 2019; Cortellini et al., 2018) have
Similar results were confirmed by Jenabian et al. (2018). Diversity of been proposed. In addition, horizontal centrifugation has also been
these findings may be explained with different PRF characteristics evaluated to improve i‐PRF with higher number and concentration
which are affected by preparation methods, application models and of platelets/leucocytes compared to fixed‐angle centrifugation. The
concentration of GFs (Jenabian et al., 2018). The results of the cur‐ optimal preparation protocol and application method of i‐PRF for use
rent study indicated that sites treated with CAF+CTG+i‐PRF showed in mucogingival treatment is yet to be determined by future studies.
a slightly higher percentage of sites (88%) with CRC compared to The increase of KTH in test and control groups of the present
sites (80%) treated with CAF+CTG. Although this single trial is not study was in agreement with several studies (Keceli et al., 2015). The
sufficient to advocate the true clinical effects of i‐PRF on recession KTH gain in the control group could be explained by the established
treatment with CAF+CTG, it can be speculated that the using i‐PRF concept that the information in the connective tissue determines the
as a “scaffold” or a “container envelop” for the CTG may enhance character of the surface epithelium (Edel, 1974; Eren & Atilla, 2014;
wound healing. Karring, Cumming, Oliver, & Löe, 1975). In addition, PRF leads to fa‐
There are two different methods of PRF application in CTG pro‐ vourable wound‐healing process in the treatment of GRs by regulat‐
cedures; PRF matrix either covers the CTG to induce a soft tissue ing proinflammatory cytokines, MMPs and MMP inhibitors at early
healing process or PRF matrix is placed under the CTG to create in‐ wound‐healing phase (Eren, Tervahartiala, Sorsa, & Atilla, 2016). A
timate contact with the periosteum or alveolar bone (Keceli et al., histological study showed good integration of the epithelial layer
2015; Keceli, Sengun, Berberoğlu, & Karabulut, 2008; Petrungaro, to the tissues with the recipient sites in CAF+PRF (Eren, Kantarcı,
2001). Basic histological studies on wound healing of free gingival Sculean, & Atilla, 2016). Furthermore, Guiha, Khodeiry, Mota, and
grafts which can also be considered for CTG healing (Zuhr, Bäumer, Caffesse (2001) revealed that the CAF+PRF group showed much
& Hürzeler, 2014) have shown that the survival of the grafts initially deeper rete pegs than the CAF+CTG group at 6 months biopsies
depends exclusively on the avascular plasmatic circulation from the (Guiha et al., 2001). These well‐developed rete pegs in the kerati‐
adjacent flaps which is followed by ingrowth of capillaries and the nized epithelial layer may provide mechanical resistance to external
formation of anastomoses between blood vessels of the recipient irritation. The increase in KTH and higher RD reduction found in the
bed and the transplanted tissues. Therefore, the application tech‐ test group of the current study may be explained by the improved re‐
nique of PRF as a membrane FM may have some disadvantages. sistance and rapid angiogenesis provided by i‐PRF which eventually
Aroca et al. (2009) have suggested that the FM form of PRF as an affects tissue proliferation and manifestation at the surgical area.
inter‐positioning membrane may form a considerable clot thickness This statement must be confirmed with further histological studies.
which may eventually restrict the collateral circulation that is essen‐ More reliable results could be achieved with a split‐mouth design
tial for CTG to re‐vascularize and heal (Aroca et al., 2009; Hwang & in the current study. In such a manner, the inter‐patient influence
Wang, 2006). Sun et al. (2014) reported that in acute myocardial in‐ on postsurgical wound healing could be diminished for both surgi‐
farction, animals treated with mesenchymal stem cells by PRF scaf‐ cal procedures. However, defect‐related characteristics, such as RD,
folds showed increased augmented angiogenesis activities, including RW, GT and KTH, were similar in both groups at baseline, minimizing
the upregulated expressions of angiogenesis factors. Therefore, the the negative effect of this factor. In addition, short follow‐up period
i‐PRF based factors which include liquid concentrate of proteins may should be considered as a limitation as 6 months may not be long
accelerate the incorporation of endothelial cells promoting rapid for‐ enough to observe clinically significant creeping attachment, which
mation of a well‐organized capillary network and revascularization may affect the results (Keceli et al., 2015). Although patients’ sub‐
while eliminating the disadvantages of a fibrin matrix‐based PRF jective aesthetic evaluation of RC has been evaluated, the lack of
application. When the i‐PRF gel is applied as a three‐dimensional colour match which is suggested to be more important than RC for
scaffold or a pouch for CTG, this framework may eventually acceler‐ subjective aesthetic assessment in mucogingival surgery (Zucchelli
ate vascularization and GFs supply between the graft and the inner et al., 2014), should be considered as a major limitation of this study.
surface of the flap. The healing potential at the intersection of the Within the limits of the present study, the following conclusions
CTG and avascular root surface may also be positively influenced by can be drawn:
this technique as the GFs may increase the mitosis of fibroblasts and
epithelial cells and accelerate the formation of a resistant connec‐ 1. Our 6‐month data comparing CAF+CTG+i‐PRF technique to
tive tissue attachment and long junctional epithelium. All of these CAF+CTG showed additional benefit in terms of KTH increase,
RD decrease (both statistically significant) and the probability Cheung, W. S., & Griffin, T. J. (2004). A comparative study of root cov‐
of obtaining CRC (though not statistically significant) for the erage with connective tissue and platelet concentrate grafts: 8‐
month results. Journal of Periodontology, 75, 1678–1687. https://doi.
treatment of deep Miller I/II GR defects affected incisors.
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J Clinic Periodontology - 2019 - Ucak Turer - Clinical Evaluation of Injectable Platelet Rich Fibrin With Connective Tissue

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Received: 25 July 2019 | Revised: 29 August 2019 | Accepted: 9 September 2019

Clinical evaluation of injectable platelet‐rich fibrin with

Onur Ucak Turer1 | Mustafa Ozcan1 | Bahar Alkaya1 | Seren Surmeli1 |

1 | I NTRO D U C TI O N predictable RC method and CTG might increase the probability of

(a) (b) (c)

(d) (e) (f)

2.4 | Initial therapy and clinical measurements

F I G U R E 2 Surgical technique in the

FIGURE 3 The CONSORT flowchart diagram of the study

CAF+CTG CAF+CTG+i‐PRF (p = .315).

Baseline 3.8 ± 1.1 4.2 ± 1.3 .162

Painkiller consumption 1,193.5 ± 459.6 1,058.8 ± 320.1 .172

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